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Characterization of amoxicillin- and clavulanic acid-specific T cells in patients with amoxicillin-clavulanate-induced liver injury.

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dc.contributor.authorKim, SH-
dc.contributor.authorSaide, K-
dc.contributor.authorFarrell, J-
dc.contributor.authorFaulkner, L-
dc.contributor.authorTailor, A-
dc.contributor.authorOgese, M-
dc.contributor.authorDaly, AK-
dc.contributor.authorPirmohamed, M-
dc.contributor.authorPark, BK-
dc.contributor.authorNaisbitt, DJ-
dc.date.accessioned2017-04-27T04:55:25Z-
dc.date.available2017-04-27T04:55:25Z-
dc.date.issued2015-
dc.identifier.issn0270-9139-
dc.identifier.urihttp://repository.ajou.ac.kr/handle/201003/13965-
dc.description.abstractDrug-induced liver injury (DILI) frequently has a delayed onset with several human leukocyte antigen (HLA) genotypes affecting susceptibility, indicating a potential role for the adaptive immune system in the disease. The aim of this study was to investigate whether drug-responsive T lymphocytes are detectable in patients who developed DILI with the combination, antimicrobial amoxicillin-clavulanate. Lymphocytes from 6 of 7 patients were found to proliferate and/or secrete interferon-gamma (IFN-γ) when cultured with amoxicillin and/or clavulanic acid. Amoxicillin (n = 105) and clavulanic acid (n = 16) responsive CD4(+) and CD8(+) T-cell clones expressing CCR, chemokine (C-C motif) receptor 4, CCR9, and chemokine (C-X-C motif) receptor 3 were generated from patients with and without HLA risk alleles; no cross-reactivity was observed between the two drug antigens. Amoxicillin clones were found to secrete a heterogeneous panel of mediators, including IFN-γ, interleukin-22 and cytolytic molecules. In contrast, cytokine secretion by the clavulanic acid clones was more restricted. CD4(+) and CD8(+) clones were major histocompatability complex class II and I restricted, respectively, with the drug antigen being presented to CD4(+) clones in the context of HLA-DR molecules. Several pieces of evidence indicate that the clones were activated by a hapten mechanism: First, professional antigen-presenting cells (APCs) were required for optimal activation; second, pulsing APCs for 4-16 hours activated the clones; and third, inhibition of processing abrogated the proliferative response and cytokine release.

CONCLUSION: Both amoxicillin- and clavulanic acid-specific T cells participate in the liver injury that develops in certain patients exposed to amoxicillin-clavulanate.
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dc.language.isoen-
dc.subject.MESHAged-
dc.subject.MESHAmoxicillin-
dc.subject.MESHAmoxicillin-Potassium Clavulanate Combination-
dc.subject.MESHCase-Control Studies-
dc.subject.MESHCell Proliferation-
dc.subject.MESHCells, Cultured-
dc.subject.MESHChemical and Drug Induced Liver Injury-
dc.subject.MESHClavulanic Acid-
dc.subject.MESHClone Cells-
dc.subject.MESHFemale-
dc.subject.MESHHumans-
dc.subject.MESHLeukocytes, Mononuclear-
dc.subject.MESHLymphocyte Activation-
dc.subject.MESHMale-
dc.subject.MESHMiddle Aged-
dc.subject.MESHReference Values-
dc.subject.MESHSampling Studies-
dc.titleCharacterization of amoxicillin- and clavulanic acid-specific T cells in patients with amoxicillin-clavulanate-induced liver injury.-
dc.typeArticle-
dc.identifier.pmid25998949-
dc.contributor.affiliatedAuthor김, 승현-
dc.type.localJournal Papers-
dc.identifier.doi10.1002/hep.27912-
dc.citation.titleHepatology (Baltimore, Md.)-
dc.citation.volume62-
dc.citation.number3-
dc.citation.date2015-
dc.citation.startPage887-
dc.citation.endPage899-
dc.identifier.bibliographicCitationHepatology (Baltimore, Md.), 62(3). : 887-899, 2015-
dc.identifier.eissn1527-3350-
dc.relation.journalidJ002709139-
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Journal Papers > Hospital > Clinical Trial Center
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